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载 5-氟尿嘧啶/依托泊苷电纺纳米纤维支架的制备及其用于局部抗黑色素瘤治疗。

Development of 5-fluorouracil/etoposide co-loaded electrospun nanofibrous scaffold for localized anti-melanoma therapy.

机构信息

Faculty of Advanced Sciences and Technology, Department of Medical Nanotechnology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

J Appl Biomater Funct Mater. 2024 Jan-Dec;22:22808000241284439. doi: 10.1177/22808000241284439.

Abstract

Nanofibrous scaffolds have emerged as promising candidates for localized drug delivery systems in the treatment of cutaneous cancers. In this study, we prepared an electrospun nanofibrous scaffold incorporating 5-fluorouracil (5-FU) and etoposide (ETP) for chemotherapy targeting melanoma cutaneous cancer. The scaffold was composed of polyvinyl alcohol (PVA) and chitosan (CS), prepared via the electrospinning process and loaded with the chemotherapeutic agents. We conducted relevant physicochemical characterizations, assessed cytotoxicity, and evaluated apoptosis against melanoma A375 cells. The prepared 5-FU/ETP co-loaded PVA/CS scaffold exhibited nanofibers (NFs) with an average diameter of 321 ± 61 nm, defect-free and homogenous morphology. FTIR spectroscopy confirmed successful incorporation of chemotherapeutics into the scaffold. Additionally, the scaffold demonstrated a hydrophilic surface, proper mechanical strength, high porosity, and efficient liquid absorption capacity. Notably, sustained and controlled drug release was observed from the nanofibrous scaffold. Furthermore, the scaffold significantly increased cytotoxicity (95%) and apoptosis (74%) in A375 melanoma cells. Consequently, the prepared 5-FU/ETP co-loaded PVA/CS nanofibrous scaffold holds promise as a valuable system for localized eradication of cutaneous melanoma tumors and mitigation of adverse drug reactions associated with chemotherapy.

摘要

纳米纤维支架已成为治疗皮肤癌的局部药物输送系统的有前途的候选者。在这项研究中,我们制备了一种包含 5-氟尿嘧啶(5-FU)和依托泊苷(ETP)的电纺纳米纤维支架,用于针对黑色素瘤皮肤癌的化学疗法。支架由聚乙烯醇(PVA)和壳聚糖(CS)组成,通过静电纺丝工艺制备,并负载有化疗药物。我们进行了相关的物理化学特性表征、评估了对黑色素瘤 A375 细胞的细胞毒性和细胞凋亡。所制备的 5-FU/ETP 共载 PVA/CS 纳米纤维支架具有平均直径为 321±61nm 的纳米纤维(NFs),形态无缺陷且均匀。傅里叶变换红外光谱(FTIR)证实了化疗药物成功掺入支架中。此外,该支架具有亲水表面、适当的机械强度、高孔隙率和高效的液体吸收能力。值得注意的是,从纳米纤维支架中观察到了持续和控制药物释放。此外,该支架显著增加了 A375 黑色素瘤细胞的细胞毒性(95%)和细胞凋亡(74%)。因此,所制备的 5-FU/ETP 共载 PVA/CS 纳米纤维支架有望成为一种有价值的系统,用于局部根除皮肤黑色素瘤肿瘤,并减轻与化疗相关的不良反应。

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